Title page for ETD etd-09192007-132236

The Effects of Macronutrient Composition on Oxidative Stress and Inflammation in Overweight and Obese Humans

Degree

PhD

Department

Human Nutrition, Foods, and Exercise

Advisory Committee

Advisor Name

Title

Rankin, Janet L. Walberg

Committee Chair

Davy, Brenda M.

Committee Member

Houston, Michael E.

Committee Member

Lee, Yong Woo

Committee Member

O'Keefe, Sean F.

Committee Member

Saker, Korinn E.

Committee Member

Keywords

postprandial inflammation

C-reactive protein

energy restriction

obesity

Date of Defense

2007-09-06

Availability

unrestricted

Abstract

Two thirds of American adults are overweight and almost half of those qualify as obese. Obesity independently increases risk for cardiovascular disease (CVD), type II diabetes (T2D), and hypertension; thus, strategies to reduce risk in this population are desperately needed. Oxidative stress and inflammation are two perpetuators of these chronic diseases that are often elevated in obesity. Interventions that target reductions in oxidative stress and inflammation may help to reduce co-morbidities associated with obesity. Weight loss is shown to reduce oxidative stress and inflammation. However, the composition of and food choices within the weight loss diet may influence the response of these factors to weight loss, and has not been adequately assessed. We first tested whether there were differential effects of a conventional low-fat, high carbohydrate weight loss diet (LF) and the Atkins diet (a popular low carbohydrate, high fat diet (HF)) on oxidative stress and inflammation. We demonstrated that HF raised C-reactive protein (CRP) levels relative to LF in overweight and obese women over four weeks. This finding raises questions as to the long term safety of the HF eating plan in terms of CVD risk. We next examined the role of oxidative stress in the HF diet-induced increase in inflammation by evaluating the effects of an antioxidant supplement versus a placebo in conjunction with HF in overweight and obese men and women. Although our full hypothesis was not supported, as oxidative stress did not increase with HF, the trend for a differential effect on CRP when antioxidants were consumed is provocative. It suggests that future research on the connection between oxidative stress, the macronutrient content of the diet, and inflammation in obesity is warranted.

Regarding the effects of specific fats, epidemiological research shows that diets high in saturated fat (SFA) are associated with higher CVD risk while diets higher in omega 3 fats (n-3FA) with lower CVD risk. However, the acute effects of these fats on indices of inflammation and oxidative stress are less understood, particularly in the overweight/obese population. As the majority of the time is spent in the postprandial state, the acute responses to high fat meals are gaining attention for their contribution to endothelial dysfunction and CVD. We showed that acute meals high in SFA increased a marker of endothelial activation (ICAM-1) which could contribute to the atherogenic associations with SFA. Conversely, including n-3FA in a high fat meal acutely enhanced NF-κB activation in circulating mononuclear cells; however, there were no increases in any inflammatory proteins measured over the 6 h postprandial period. It is apparent that dietary macronutrients can influence factors associated with chronic disease in overweight and obese individuals. The evidence presented here may help to refine dietary recommendations for this population.